Claims
- 1. A process for the production of (S)-N-tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxyamide, comprising:a) reacting (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid with triphosgene in dioxane to form an N-carboxyanhydride of the following formula b) reacting the N-carboxyanhydride with tert-butylamine in toluene to produce the (S)-N-tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxyamide.
- 2. The process of claim 1, wherein step a) is carried out at temperatures within the range of from +20 to +105° C.
- 3. The process of claim 1, wherein the (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is reacted in step a) at an initial concentration of from 0.3 to 2.0 m/l.
- 4. The process of claim 1, wherein the (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is reacted in step a) at an initial concentration of from 0.5 to 1.5 m/l.
- 5. The process of claim 1, wherein the (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is reacted in step a) with from 0.3 to 0.2 equivalents of triphosgene.
- 6. The process of claim 1, wherein the (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is reacted in step a) with triphosgene under reflux.
- 7. The process of claim 1, wherein step b) is carried out at temperatures within the range of from −20 to +30° C.
- 8. The process of claim 1, wherein the N-carboxyanhydride is reacted in step b) with from 1 to 10 equivalents of tert-butylamine.
- 9. The process of claim 1, wherein the (S)-N-tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxyamide product is isolated by crystallization.
- 10. The process of claim 1, wherein step b) is carried out at temperatures within the range of from −10 to +5° C.
- 11. The process of claim 1, wherein the N-carboxyanhydride is reacted in step b) with from 3 to 5 equivalents of the tert-butylamine.
- 12. A process for the production of (S)-N-tert-butyl-1,2,3,4-tetrahydroisoquinoline 3-carboxyamide, comprising:a) reacting (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid at an initial concentration of 0.3 to 2 m/l. with from 0.3 to 1.2 equivalents of triphosgene, in dioxane and at temperatures within the range of from +20° to 105° C., to form an N-carboxyanhydride of the following formula b) reacting the N-carboxyanhydride with tert-butylamine in toluene to produce the (S)-N-tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxyamide.
- 13. The process of claim 12, wherein the (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is reacted in step a) with triphosgene under reflux.
- 14. A process for the production of (S)-N-tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxyamide, comprising:a) reacting (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid with triphosgene in dioxane to form an N-carboxyanhydride of the following formula b) reacting the N-carboxyanhydride with from 1 to 10 equivalents of tert-butylamine, in toluene and at temperatures within the range of from −20° to 30° C., to produce the (S)-N-tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxyamide.
- 15. A process for the production of (S)-N-tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxyamide, comprising:a) reacting (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid at an initial concentration of 0.3 to 2 m/l. with from 0.3 to 1.2 equivalents of triphosgene, in dioxane and at temperatures within the range of from +20° to 105° C., to form an N-carboxyanhydride of the following formula b) reacting the N-carboxyanhydride with from 1 to 10 equivalents of tert-butylamine, in toluene and at temperatures within the range of from −20° to 30° C., to produce the (S)-N-tert--butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxyamide.
- 16. The process of any of claims 12, 14 or 15, wherein the (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is reacted in step a) with triphosgene under reflux.
Priority Claims (1)
Number |
Date |
Country |
Kind |
MI98A1478 |
Jun 1998 |
IT |
|
Parent Case Info
This Application is a continuation of PCT/E99/04266 filed Jun. 17, 1999.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5587481 |
Allen et al. |
Dec 1996 |
A |
Foreign Referenced Citations (1)
Number |
Date |
Country |
0 751 128 |
Jan 1997 |
EP |
Non-Patent Literature Citations (1)
Entry |
The Merck Index, Twelfth Edition, pp. 1438-39, 1996. |
Continuations (1)
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Number |
Date |
Country |
Parent |
PCT/EP99/04266 |
Jun 1999 |
US |
Child |
09/478690 |
|
US |